The invention relates to hypoxic cell radiation sensitizers that have high radiosensitizing activity and selectivity for hypoxic cells.
Hypoxic cells are relatively resistant to killing by radiation. To achieve the same proportion of cell kill, about three times the radiation dose is required as for well oxygenated cells. Oxygen has the ability to sensitize cells to ionizing radiation at clinically useful radiation doses. Coleman, Journal of the National Cancer Institute Vol. 80, No. 5 pp. 310-317 (1988) describes hypoxia in tumors and various approaches to treatment of hypoxic cells.
U.S. Pat. No. 4,603,133 relates to esters, amides and N-substituted amides of 2-[N- (morpholinoalkyl)aminosulfonyl]-6-nitrobenzoic acids, used as sensitizers of hypoxic tumor cells to therapeutic radiation. That patent also relates to 2-chlorosulfonyl-6-nitrobenzoate ester prepared as described in U.S. Ser. No. 716,886 filed March 27, 1985 and aminating said 2-chlorosulfonylbenzoate ester to produce the corresponding sulfamyl or N-substituted sulfamylnitrobenzoic esters.
U.S. Ser. No. 937,275, filed Dec. 3, 1986, describes 3-nitrobenzenesulfonamides useful in enhancing the effect of therapeutic radiation.
U.S. Ser. No. 937,277, filed Dec. 3, 1986, describes 2-(substituted sulfamyl) derivatives of 4-nitrobenzamide useful for increasing the sensitivity of hypoxic cancer cells to X-rays and gamma-radiation.
U.S. Pat. No. 4,731,369 describes amides and esters of 2-(N-(hydroxypiperidinoalkyl) and (hydroxypyrrolidinoalkyl)-aminosulfonyl)-6-nitrobenzoic acids which are useful for treating patients in need of therapeutic radiation.